myelin-basic-protein and Neoplasms

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor that is activated by fibrillar collagens. Here, we review the expression and role of DDR1 in the central nervous system (CNS). In a murine model, DDR1 is expressed in oligodendrocytes in the developing brain and during remyelination. In human adult brain tissue, DDR1 is detected in a similar pattern as other classical myelin proteins such as myelin basic protein (MBP). Up to 50 transcripts of DDR1 have been detected in human tissues, of which 5 isoforms have been identified. In the human brain, all 5 isoforms are detectable, but DDR1b is the most highly expressed, and DDR1c is coexpressed with myelin genes. DDR1 sequence variants have been associated with psychiatric disorders, and upregulation of this gene occurs in gliomas. Moreover, mutations in DDR1 have been found in tumors of Schwann cells, which are the myelinating cells of the peripheral nervous system. All these data suggest that DDR1 plays a role in myelination and is relevant to neuropsychiatric diseases.

Topics: Animals; Astrocytes; Brain; Central Nervous System; Discoidin Domain Receptor 1; Endothelial Cells; Humans; Mice; Microglia; Myelin Basic Protein; Myelin Proteins; Neoplasms; Oligodendroglia; Protein Isoforms; RNA, Messenger; Up-Regulation

The role of holocarboxylase synthetase (HLCS) in catalyzing the covalent binding of biotin to the five biotin-dependent carboxylases in humans is well established, as are the essential roles of these carboxylases in the metabolism of fatty acids, the catabolism of leucine, and gluconeogenesis. This review examines recent discoveries regarding the roles of HLCS in assembling a multiprotein gene repression complex in chromatin. In addition, emerging evidence suggests that the number of biotinylated proteins is far larger than previously assumed and includes members of the heat-shock superfamily of proteins and proteins coded by the ENO1 gene. Evidence is presented linking biotinylation of heat-shock proteins HSP60 and HSP72 with redox biology and immune function, respectively, and biotinylation of the two ENO1 gene products MBP-1 and ENO1 with tumor suppression and glycolysis, respectively.

Topics: Biomarkers, Tumor; Biotin; Biotinylation; Carbon-Nitrogen Ligases; DNA-Binding Proteins; Gene Expression; Gene Expression Regulation; Glycolysis; Heat-Shock Proteins; Humans; Myelin Basic Protein; Neoplasms; Phosphopyruvate Hydratase; Tumor Suppressor Proteins

Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.

Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Antigens; Carcinoma; Central Nervous System Diseases; Chorionic Gonadotropin; Cytoskeleton; Desmin; Factor VIII; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Immunoglobulins; Intermediate Filament Proteins; Keratins; Lymphoma; Medical Oncology; Meningeal Neoplasms; Myelin Basic Protein; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neurology; Oligodendroglia; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma; Vascular Diseases; Vimentin; von Willebrand Factor

It is proposed that some cases of depressive illness in cancer patients may be caused by immunological interference with the activity of serotinin, one of the neurotransmitters thought to be implicated in depression. This interference could be mediated in two ways. Antibody induced against a protein released from cancer cells could, on the basis of cross-reactivity with CNS tissue, bind to receptors for serotonin and block them. Such primary antibodies could stimulate the production of anti-idiotypic antibodies, which would act as an alternative receptor for serotonin and reduce its synaptic availability.

Topics: Animals; Antigens, Neoplasm; Autoimmune Diseases; Brain; Cross Reactions; Depressive Disorder; Guinea Pigs; Humans; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Rabbits; Receptors, Serotonin; Serotonin

Topics: Antigen-Antibody Reactions; Antigens, Neoplasm; Cell Migration Inhibition; Cytoplasm; Electrophoresis; Humans; Lymphocytes; Macrophages; Methods; Myelin Basic Protein; Neoplasm Proteins; Neoplasms

In vitro cell-mediated immunity was assayed by leukocyte adherence inhibition (LAI) to determine the extent of autosensitization to myelin basic protein (MBP). Leukocytes from 123 cancer patients, 16 patients freed of cancer, 135 patients with benign disease, and 26 patients with destruction of nervous parenchyma were tested. Most patients with cancer reacted to MBP: 92%, 93%, 82%, 78%, 75% and 62% for pancreatic, colonic, esophageal, lung, ovarian and breast. Few patients with benign diseases reacted to MBP. Patients with multiple sclerosis (MS) were sensitized to MBP, but patients with other nervous tissue injury did not react to MBP. Cancer patients did not remain sensitized to MBP once they were freed of their cancer. The LAI assay is a straightforward method of measuring cellular autosensitivity to MBP. In the population of patients tested, autosensitivity to MBP was confined, except for MS, principally to cancer patients.

Topics: Autoantigens; Breast Neoplasms; Dose-Response Relationship, Immunologic; Humans; Immunologic Techniques; Intestinal Polyps; Leukocyte Adherence Inhibition Test; Multiple Sclerosis; Myelin Basic Protein; Neoplasms; Pancreatic Neoplasms; Pancreatitis

Patients' leukocytes were shown to react consistently in tube leukocyte adherence inhibition (LAI) assays with myelin basic protein (MBP) at optimal concentration, whereas control leukocytes were nonreactive. Mononuclear cells from patients with cancer gave positive LAI reactions with MBP, but separated T-lymphocytes, monocytes, and neutrophils did not. The mononuclear cell LAI responses were blocked by monoclonal antibody (MAb) to monomorphic determinant of class II major histocompatibility complex (MHC) antigens and to T4+ (Leu-3a+) and T3+ (Leu-4+) T-cell differentiation antigens but not by antibody to class I MHC antigens or T8+ (Leu-2a+) antigens. MBP was thus recognized by helper T-cells, requiring presentation in association with class II MHC determinants on monocytes. MAb to class I and class II MHC antigens and to T8+ (Leu-2a+), T4+ (Leu-3a+), and T3+ (Leu-4+) differentiation antigens did not negate LAI mediated by peripheral blood lymphocytes to organ-specific cancer neoantigens (OSN) of crude extracts of allogeneic cancer, which had previously been shown to react with cytophilic antibody on allogeneic monocytes. When membrane OSN and leukocytes were autologous, T8+ (Leu-2a+) phenotypic T-cells also mediated LAI that was blocked by anti-T8 (Leu-2a) and anti-T3 (Leu-4). LAI induced by MBP was also negated by drugs that antagonize thromboxane-leukotriene biosynthesis, indicating that, in common with other LAI reactions, the terminal mediators of nonadherence are oxidative metabolites of arachidonic acid. In addition to clarifying the role of MBP in the cellular in vitro immunoreactivity of cancer patients, the present observations have important implications for theories of LAI. Sensitized leukocytes have different mechanisms for the recognition of antigens in different forms, and the antigen-stimulated leukocytes produce mediators that in a final common pathway induce nonadherence of surrounding cells through leukotriene-like metabolites.

Topics: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Arachidonic Acid; Arachidonic Acids; Dose-Response Relationship, Immunologic; Histocompatibility Antigens; Humans; Leukocyte Adherence Inhibition Test; Major Histocompatibility Complex; Monocytes; Myelin Basic Protein; Neoplasms; Neutrophils; T-Lymphocytes

Phytohaemagglutinin (PHA), a well-known mitogen, and encephalitogenic factor (EF) are recognized by lymphocytes of patients with different malignant diseases as non-specific antigens. Utilizing these two antigens, the SCM (structuredness of the cytoplasmatic matrix) test offers a means of discrimination between malignant and non-malignant diseases. The SCM test can also be used as a specificity test since lymphocytes from donors with a given malignant disease react exclusively with the tumour-associated antigen (TAA) of that disease. Results from 73 donors (15 healthy patients, 38 patients with different types of malignant disorders and 20 patients with autoimmune diseases) indicate the predictive value of the test. First, the non-specific test was applied in order to establish whether the patients suffered from an active malignant disease. The lymphocytes of those patients which were found to suffer from an active malignant disorder were then exposed to different types of tumour tissues. Twenty-five out of the 38 patients with malignant disorders were found by the SCM test to have an active disease. The lymphocytes of 24 out of these 25 patients showed a positive reaction when exposed to tumour tissue of the same type of cancer of which they were found to suffer by other clinical tests, and displayed no reaction with any other tumour tissues for which they were tested. One patient, with an inconclusive value of the SCM test, showed no reaction with any type of tumour to which he was exposed. The remaining 13 patients, who were diagnosed by the test as non-cancerous, did not show any clinical evidence of malignancy at the time of the test, after their tumours had been excised. Eighteen out of 20 patients with autoimmune diseases showed negative results when tested by the general test and by the various specificity tests.

Topics: Antigens, Neoplasm; Breast Neoplasms; Colonic Neoplasms; Epitopes; Fluorescence Polarization; Humans; Lymphocyte Activation; Lymphocytes; Myelin Basic Protein; Neoplasms; Phytohemagglutinins

Leucocytes from 4 cancer patients showed cellular reactivity in the leucocyte adherence inhibition (LAI) assay in the presence of the synthetic encephalitogenic peptide of human myelin basic protein. All patients exhibited reactivity at a peptide concentration of 500 ng/ml. Leucocytes from 4 non-cancer patients failed to react. Suppression of LAI was detected in all 4 cancer patients by adding their serum to reactive mixtures containing peptide and autologous leucocytes. Each serum was subjected to column chromatography on Sephacryl S-200 to determine the molecular weight distribution of suppressive (blocking) factors. The greatest suppression was found in all cases within the range 90-155 kdalton.

Topics: Aged; Antigens, Neoplasm; Female; Humans; Immunity, Cellular; Immunologic Techniques; Intestinal Neoplasms; Leukocyte Adherence Inhibition Test; Lung Neoplasms; Lymphocytes; Middle Aged; Myelin Basic Protein; Neoplasms; Ovarian Neoplasms; Urinary Bladder Neoplasms

Topics: Fluoresceins; Fluorescence Polarization; Humans; Lymphocyte Activation; Myelin Basic Protein; Neoplasms; Phytohemagglutinins

Upon incubation with human encephalitogenic protein (HEP) blood lymphocytes from patients with malignant tumours release mediators (lymphokines) leading to a decreased electrophoretic mobility of guinea pig peritoneal macrophages. The lymphocyte supernatants used for incubating the macrophages contain HEP, nonspecific lymphocyte-derived proteins, and in case of sensitized lymphocytes also specific mediators. Whereas HEP or nonspecific lymphocyte products do not themselves exert any effect on macrophages, they produce a nonspecific mobility reduction when acting simultaneously. In the presence of 2.4% (v/v) dimethylsulfoxide (DMSO) this nonspecific effect is prevented. The specific lymphokine action, however, remains stable in the presence of DMSO. It cannot be decided whether DMSO exerts its effect via the membrane of macrophages or/and by influencing the interactions of proteins in the soluble phase.

Topics: Animals; Cell Movement; Dimethyl Sulfoxide; Electrophoresis; Guinea Pigs; Humans; Lymphocytes; Lymphokines; Macrophages; Myelin Basic Protein; Neoplasms

The leukocyte migration inhibition test in agarose technique was standardized as far as possible. The greatest interassay variance is not more than 10%, the greatest intraassay variance less than 5%. The test was carried out as a two-step technique in a homologous system. Such variances have not been obtained when an autologous system was used. Myelin basic protein was used as antigen. Migration inhibitions greater than 43% were measured in 66% of the controls (22 healthy persons, 22 patients with non malignant diseases), 30% of the patients with malignancies showed migration inhibitions of more than 43% (36 tumor patients without evidence of disease, 27 patients with tumors in progression). These results may reflect a stimulation of the lymphocytes by using myelin basic protein as antigen under the conditions we have used.

Topics: Cell Migration Inhibition; Granulocytes; Humans; Leukocytes; Lymphocytes; Myelin Basic Protein; Neoplasms

The primary reaction of the macrophage electrophoretic mobility test (MEM) and its modifications (viz. the interaction of myelin basic protein (MBP) and mononuclear cells) has been investigated. The binding of MBP to mononuclear cells is rather weak, and on incubation with mononuclear cells the MBP is proteolytically degraded. A fast process leads to fragments with mol. wts in the range 9000-14,000, followed by a slower process leading to peptides smaller than 5000. Both binding and proteolytic degradation are the same for mononuclear cells from cancer patients and from control individuals.

Topics: Electrophoresis, Polyacrylamide Gel; Humans; Kinetics; Lymphocytes; Molecular Weight; Monocytes; Myelin Basic Protein; Neoplasms; Protein Binding

It is reported about first results of the immunologic evidence of E.N.R. tumors with the help of MEM-tests with application of HEP as antigen. The findings of 31 patients with tumours in the E.N.T. area are confronted with the results obtained from 116 tumour-free control persons and 108 patients with other swelling localisations. The sensitivity of the examinations of E.N.T. tumours was 89.3 p.c., i.e. especially favourable.

Topics: Antibodies, Neoplasm; Antigens, Neoplasm; Electrophoresis; Humans; Macrophages; Myelin Basic Protein; Neoplasms; Otorhinolaryngologic Diseases

Fluorescence polarization measurement during the progress of fluorochromasia has been used to study the response of human lymphocytes to phytohaemagglutinin (PHA) and to tumour-associated antigens, as a basis for the detection of malignant disease. Polarization (P) values of both stimulated and unstimulated lymphocytes decreased with increasing intracellular fluorescence intensity, and with the duration of the fluorochromatic reaction. When these effects were taken into account, there was no significant difference in the change of P following stimulation of lymphocytes from 50 cancer patients or healthy subjects; the magnitude of the response was related more to the age of the donor and to the extent of granulocyte contamination of the lymphocyte preparation than to the presence of cancer. There were, however, significant differences in the change in leakage of fluorescein out of the lymphocytes and in the change in hydrolysis rate after PHA stimulation between lymphocytes from healthy individuals and from patients with cancer.

Topics: Adult; Aged; Antigens, Neoplasm; Blood Sedimentation; Fluoresceins; Fluorescence Polarization; Humans; Hydrolysis; Lymphocyte Activation; Lymphocytes; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Phytohemagglutinins; Time Factors

Tables are presented showing data collected to date on the clinical trials of the macrophage electrophoretic mobility test for cancer of Field and Caspary. Seven variations on the original technique are summarized. The original antigen used in these tests was the basic protein of CNS myelin. Four additional proteins have been shown to function in these tests in place of the basic protein. There appears not to be a strong immunological crossreaction between these proteins. This paper discusses a possible solution to the problem of why non-crossreactive proteins appear to crossreact when testing cancer patients with the macrophage electrophoretic mobility related tests. All lymphocytes in saline suspension without added protein will aggregate. This is prevented in normals by the addition of some proteins to the culture, but is not so prevented in cancer and other diseases. Aggregation results in lymphokine release that makes the macrophage electrophoretic mobility test and variants positive. Aggregation occurs in the first incubation step of these tests and this non-immunological aggregation is the underlying phenomenon detected rather than specific antigen recognition as has been heretofore presumed.

Topics: Antigens, Neoplasm; Cell Aggregation; Cell Movement; Histones; Humans; Immunologic Techniques; Lymphocytes; Lymphokines; Macrophages; Myelin Basic Protein; Neoplasms

The SCM test was established as originally described, and an attempt was made to evaluate it using myelin basic proteins. Various later modifications described by the original authors were incorporated as they were communicated to us. In separate studies attempts were also made to overcome some of the problems which seemed inherent in the technique. In the small series for which valid results were obtained we were unable to confirm the original claim that the method discriminates between cancer patient lymphocytes and those from non-cancer subjects with almost 99% reliability. Indeed, although differences were found between the mean SCM values of cancer patients and of healthy controls, these differences were not significant.

Topics: Cells, Cultured; Cytoplasm; Evaluation Studies as Topic; Fluorescence Polarization; Humans; Lymphocytes; Myelin Basic Protein; Neoplasms; Phytohemagglutinins; Rosette Formation

Theoretical aspects are considered on the requirements of immunological cancer tests. The criteria of clinical applicability are: Specificity, sensitivity, information with respect to tumour localisation. Immunodiagnostic tests cover the following areas: Early diagnosis on the basis of screening of the whole population or of risk groups, differential diagnosis, detection of relapse or metastases, prognosis. Experimental results are presented on a test for tumour detection. In a blind test study patients with clinically manifest tumours were recognized in about 80--90%, when using human fetal extract as antigen in the macrophage-electro-phoretic-mobility technique.

Topics: Antigens; Diagnosis, Differential; Fetus; Humans; Macrophages; Mass Screening; Myelin Basic Protein; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Serologic Tests; Tissue Extracts

Lymphocytes from seven patients with malignancies, from seven patients with non-malignancies, and from five healthy persons were incubated with 125I-labeled MBP. Binding of MBP of lymphocytes was monitored from 0.5 to 20h. The binding ranged from 4 to 7% of the total MBP present and remained fairly constant during the first 4h of incubation. It dropped considerably at 20h. Mean percentages of MBP binding were lower in cancer patients than in persons without malignancies. After incubation, the supernates were examined by gel electrophoresis. The electrophoretic pattern was similar in comparing groups with different diagnoses. A considerable loss of MBP in the terminal supernatant (20h) was found. When tested in the electrophoretic mobility test (EM test) with stabilized erythrocytes, supernatant derived from cancer patients produced a somewhat higher mean slowing effect than did superntes from other patients and controls.

Topics: Electrophoresis, Polyacrylamide Gel; Erythrocytes; False Positive Reactions; Hematologic Tests; Humans; Lymphocytes; Myelin Basic Protein; Neoplasms

Simplified agarose-coated capillary microelectrophoresis was adapted to the Macrophage Electrophoretic Mobility (MEM) test for cancer detection. Guinea pig alveolar macrophages gave superior reproducibility to peritoneal macrophages. As good or better reproducibility was obtained with cryopreserved, as with fresh macrophages. The electrophoretic mobilities of patients' lymphocytes themselves, after incubation with Encephalitogenic Factor (EF) showed a significant increase in electrophoretic mobility, while in control lymphocytes a decrease occurred. Thus, for the detection of the results of the interaction of EF on human lymphocytes, a direct lymphocyte electrophoretic mobility test may suffice, and guinea pig macrophages may no longer be required at all.

Topics: Animals; Cell Movement; Electrophoresis, Cellulose Acetate; Guinea Pigs; Humans; Lymphocytes; Macrophages; Myelin Basic Protein; Neoplasms

Sensitivity to human encephalitogenic factor (EF) was measured in 70 cancer patients, in 34 patients with various non-malignant diseases and in 18 healthy volunteers, using the macrophage migration inhibition (MMI) test. Sensitization was demonstrated in 44/70 (63%) of the cancer patients, in 11/34 (32%) of the patients with non-malignant conditions and in one (5%) of the healthy individuals. No significant difference was seen in the frequency of demonstrable sensitivity with clinical stage of disease in cancer patients.Autologous serum from cancer patients had the ability to abrogate EF-mediated migration inhibition in 22/30 sensitized individuals. This blocking occurred with a similar frequency in all 3 clinical stages of cancer. Autologous serum from patients with non-malignant disease caused abrogation of EF-mediated migration inhibition in 4/11 sensitized individuals, whilst none of the healthy control individuals showed any significant change in the migration index in the presence of autologous serum. Homologous serum from patients with carcinoma of the breast or lung with and without autologous blocking activity and serum from a healthy individual were tested against lymphocytes from patients with various tumour types with the MMI test. Of 11 patients tested in the absence of serum, 8 (73%) showed significant migration inhibition with EF, whilst serum from patients with carcinoma of the lung or breast with autologous blocking activity abolished migration inhibition with EF in all 8 individuals with the former and in 6 with the latter, regardless of the tumour type from which the lymphocytes under test were derived. Homologous serum from both a carcinoma of the lung and breast without autologous blocking activity did not abolish migration inhibition with EF, except with the latter in one patient with a carcinoma of the lung.

Topics: Adolescent; Adult; Aged; Blood; Cell Migration Inhibition; Female; Humans; Immunity, Cellular; Lymphocytes; Macrophages; Male; Middle Aged; Myelin Basic Protein; Neoplasms

Topics: Adult; Brain Diseases; Child; Diagnosis, Differential; Electrophoresis; Erythrocytes; False Negative Reactions; False Positive Reactions; Humans; Immunization; Lymphocytes; Macrophages; Myelin Basic Protein; Neoplasms; Nerve Degeneration

When peripheral lymphocytes from patients with a history of cancer are incubated with encephalitogenic factor (EF), in 90% of cases the resulting products reduce the net surface negativity of guinea-pig macrophages, used as detector cells, as revealed in the macrophage electrophoretic mobility (MEM) test. The MEM test is positive in 36% of people with no history of cancer. Formaldehyde-fixed tanned sheep erythrocytes have been used as detector cells in place of guinea-pig macrophages, in a fixed tanned erythrocyte electrophoretic mobility (FTEEM) test, with lymphocyte products identical to those used in MEM tests. In patients with a history of cancer, positive results were obtained in 28/42 cases with the FTEEM test compared with 32/42 in the MEM test. In people with no history of cancer, negative results were obtained in 16/18 cases with the FTEEM test, compared with 12/18 in the MEM test in the present series, and 51/69 in a more extensive series. These differences are not significant. Cases in which discrepancies are revealed between the two tests are discussed in terms of individual case histories.

Topics: Animals; Cell Movement; Electrophoresis; Erythrocytes; Guinea Pigs; Humans; Hydrolyzable Tannins; Lymphocytes; Macrophages; Methods; Myelin Basic Protein; Neoplasms; Sheep

Lymphocyte sensitisation to encephalitogenic factor (EF) was determined in 131 children with the electrophoretic mobility test (EM-test) to find out, whether this test may be helpful in the diagnosis of malignant disease in children. None of 34 healthy controls showed a decrease of electrophoretic mobility of more than 5%, while all 10 children with malignant solid tumors showed a slowing of more than 5%. 3 of 54 patients with non malignant disease showed a slowing of more than 5% in the EM-test. Children with malignant solid tumors during therapy and children with leukemia during different stages of the disease often showed a slowing of less than 5% in the EM-test. The possible diagnostic help of the EM-test is shown in a case history. Finally some technical remarks are made on improving this test, and further studies are suggested.

Topics: Cell Movement; Child; Electrophoresis; Epilepsy; Humans; Infectious Mononucleosis; Leukemia, Lymphoid; Lymphocytes; Myelin Basic Protein; Neoplasms

Leukocyte migration tests under agarose (Clausen technique) were performed in 28 patients tentatively diagnosed as having any malignancy with the use of a 3 M KCl-extract panel prepared from bronchogenic, gastric, colonic, renal, and mammary carcinoma, corresponding normal tissues, carcinoembryonic antigen (CEA), and human encephalitogenic protein (HEP). 17 out of 22 proven carcinoma patients showed sensitization by reaction with optimal concentrated KCl-extract of cancer from the same organ type as their own tumor. In some cases positive reactions could be observed also with normal tissue antigen (NTA) of tumor organ type (7/22) or with an additional carcinoma extract of organ type differing from patients own primary tumor (8/22). Gastrointestinal carcinomas, especially, showed sensitization to CEA (7/12) contrary to nongastrointestinal carcinomas (1/10). With HEP no positive reactivity could be found (0/10). With the use of tumor antigen panel (5 antigens) only few positive reactions (MI less than 0.80 or greater than 1.20) could be observed in 6 patients with nonmalignant diseases (1/30 tests) and 8 healthy blood donors (1/40 tests). A widespread individual screening program using tissue antigens for patients suspected of malignancies could give a pattern of reactivities and improve the recognition of cell-mediated sensitization against tumor tissues.

Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoembryonic Antigen; Cell Migration Inhibition; Colonic Neoplasms; Epitopes; Female; Humans; Immunity, Cellular; Kidney Neoplasms; Leukocytes; Lung Neoplasms; Male; Middle Aged; Myelin Basic Protein; Neoplasms; Sepharose; Stomach Neoplasms

The macrophage electrophoretic mobility (MEM) test provides a highly sensitive in vitro technique for the detection of cell-mediated immunity in man. The principle involved is the lymphokine-mediated reduction of the negative surface charge of guinea pig macrophages shown by the slowing of the macrophages during cell electrophoresis. Lymphocytes from 162 patients were tested by MEM. They were exposed to a battery of KCl extracts from normal and malignant human tissues, to encephalitogenic protein (EP), to carcinoembryonic antigen (CEA), and to thyroglobulin. Variable lymphocyte responses to EP, CEA and KCl extracts from different cancers gave MEM reaction profiles common to patients with carcinomas of the same organ origin.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Movement; Cross Reactions; Electrophoresis; Female; Humans; Immunity, Cellular; Lymphocytes; Macrophages; Myelin Basic Protein; Neoplasms; Organ Specificity; Surface Properties; Thyroglobulin

A modified electrophoretic mobility (EM) test was performed in 150 children to examine their lymphocyte sensitization to myelin basic protein (encephalitogenic factor). Measurements in the cytopherometer were facilitated by using devitalized sheep erythrocytes as indicator particles instead of macrophages. A significant decrease in EM was found in 29/30 children with acute lymphoblastic leukaemia and in 67/75 children with solid tumours, thus giving a false negative rate in malignant disease of 9/105=8-6%, as compared to 6 false positives among 45 children with non-malignant disorders; 5 of the later "false/positive" 6 patients had autoimmune disease. Results of the EM test in the children with leukaemia were compared with those in 9 patients with non-Hodgkin's lymphoma and 2 with Hodgkin's disease at different stages, but no striking change was seen between different diseases, or after cessation of long-term immunosuppressive chemotherapy. Percentage of "slowing" ranged from 4 to 30%. These results indicate that patients with lymphoid malignancies still have lymphocytes which had been sensitized by a common antigen of the malignant cell clone at the beginning of the disease. The EM test, furthermore, could serve as an additional diagnostic aid in differentiating benign from malignant masses in the abdomen, extremities or intracranial disease.

Topics: Abdominal Neoplasms; Acute Disease; Antigens; Child; Electrophoresis; Humans; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasms

Topics: Dose-Response Relationship, Drug; Electrophoresis; Humans; Lymphocyte Activation; Lymphocytes; Myelin Basic Protein; Neoplasms

Lymphocyte sensitization to myelin basic protein (encephalitogenic factor, EF) was determined in 193 children by measuring the electrophoretic mobility of indicator particles which had been incubated with the supernatant of the lymphocyte-antigen (EF) mixture. A significant decrease in electrophoretic migration time was found in 77 of 85 children with malignant tumours localized in brain, abdomen and extremities, in 36 of 38 children with acute lymphoblastic leukaemia (all except one in hematological remission), and in all 17 patients with lymphoma, in contrast to only 1 of 10 healthy children and 14 of 48 patients with non-malignant disorders. 10 of these 14 "false positive" patients, however, had auto-immune diseases. Thus, with false negative and false positive rates of less than 10%, this test could be of diagnostic help in patients with suspected malignant or auto-immune disease. Two examples of preoperative application of the EM-test are demonstrated.

Topics: Abdominal Neoplasms; Adolescent; Age Factors; Autoimmune Diseases; Brain Neoplasms; Cell Movement; Child; Electrophoresis; Humans; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasms

A control series of 105 patients in hospital with non-malignant diseases was used in a limited clinical assessment of the MOD-MEM test. Twenty-seven positive results could be explained on the basis of destruction of nervous parenchyma, tissue necrosis, tuberculosis, malignant disease, etc. The remaining 13 unexplained positives showed a sex and age distribution in agreement with that predicted from cancer registration statistics if the MOD-MEM test detects cancer about 16 years before the clinical appearance of the disease.

Topics: Evaluation Studies as Topic; Female; Humans; Immunologic Techniques; Lymphocytes; Macrophages; Male; Myelin Basic Protein; Neoplasms; Time Factors

Topics: Adult; Antigens, Neoplasm; Cell Migration Inhibition; Cross Reactions; Female; HeLa Cells; Humans; Immunity, Cellular; Male; Middle Aged; Myelin Basic Protein; Neoplasms; Nervous System Diseases; Serotonin

The specific lymphocyte sensitization of patients with malignant diseases against a basic protein, isolated from human brain, was studied by the lymphocyte migration inhibition technique. A sensitization of lymphocytes of cancer patients against this encephalitogenic factor (EF) was first reported by FIELD and CASPARY in 1970. Their test system was the Macrophage-Electrophoretic-Mobility-Test (MEMT). In 17 out of 18 patients with malignant disease we found a specific inhibition or enhancement of the migration area of lymphocytes more than 15%.

Topics: Carcinoma, Bronchogenic; Cell Migration Inhibition; Humans; Intestinal Neoplasms; Lung Neoplasms; Lymphocyte Activation; Lymphoma; Macrophages; Male; Melanoma; Myelin Basic Protein; Neoplasms; Stomach Neoplasms

Lymphocytes from patients with neoplastic disease were tested for sensitization to encephalitogenic factor (EF) by the macrophage migration inhibition test. Sensitization to EF was demonstrated in 71% of patients with various forms of neoplastic disease. Sensitization to EF was also demonstrated for 31% of subjects with no evidence of neoplastic disease; these included patients with warts, chronic bronchitis and hernias. In contrast, healthy subjects showed no sensitization to myelin basic protein. These observations suggest that sensitization to EF may not be confined to patients with neoplastic disease. Lymphocytes from hamsters bearing a transplanted virus induced tumour were sensitized to EF prepared from both human and hamster brain. Sensitization was also seen in hamsters infected with influenza virus but not in animals with acute tubular necrosis produced by glycerol treatment. The development of an animal model system provides a method for the investigation of possible mechanisms of sensitization.

Topics: Animals; Brain; Bronchitis; Cell Migration Inhibition; Cricetinae; Disease Models, Animal; Hernia; Humans; Immunity, Cellular; Influenza, Human; Kidney Tubular Necrosis, Acute; Macrophages; Myelin Basic Protein; Neoplasms; Neoplasms, Experimental; Warts

Topics: Humans; Lymphocyte Activation; Lymphocytes; Myelin Basic Protein; Neoplasms

Macrophage migration inhibition (MMI) tests have been carried out using lymphocytes from twenty-six patients with malignant disease and from twenty-two other subjects. The antigens used were the same as those employed in the macrophage electrophoretic mobility (MEM) test. The results indicate that the inforation obtained using the MMI test is similar to that found with the MEM test.

Topics: Adult; Aged; Animals; Antigens; Antigens, Neoplasm; Cell Migration Inhibition; Female; Guinea Pigs; Humans; Lymphocyte Activation; Macrophages; Male; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Neoplasms

Topics: Cytoplasm; Fluorescence; Humans; Lectins; Leukemia, Lymphoid; Lymphocytes; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Precancerous Conditions

Changes in the structuredness of the cytoplasmic matrix (SCM) of human lymphocytes induced by PHA, CaBP and EF were studied with the technique of fluorescence polarization. The study suggests that the SCM test may offer a new and fast technique for the detection of malignant growth.

Topics: Adolescent; Adult; Aged; Antigens, Neoplasm; Cytoplasm; Female; Humans; Lectins; Lymphocytes; Male; Methods; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Spectrometry, Fluorescence

Topics: Animals; Binding Sites, Antibody; Binding, Competitive; Humans; Hypersensitivity, Delayed; Immune Sera; Immunoglobulin alpha-Chains; Immunoglobulin epsilon-Chains; Immunoglobulin Fab Fragments; Immunoglobulin gamma-Chains; Immunoglobulin lambda-Chains; Immunoglobulin mu-Chains; Macrophages; Myelin Basic Protein; Neoplasms; Pollen; Rabbits; T-Lymphocytes; Tetanus Toxoid

Topics: Animals; Antigens, Neoplasm; Cell Migration Inhibition; Electrophoresis; Guinea Pigs; Humans; Lymphocytes; Macrophage Migration-Inhibitory Factors; Macrophages; Mice; Myelin Basic Protein; Neoplasms

Topics: Adult; Aged; Animals; Antigens; Antigens, Neoplasm; Cell Migration Inhibition; Cells, Cultured; Child; Electrophoresis; Female; Guinea Pigs; Humans; In Vitro Techniques; Macrophages; Male; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Neoplasms

Topics: Animals; Antigens, Neoplasm; Asthma; Cell Migration Inhibition; Diagnostic Errors; Electrophoresis; Female; Guinea Pigs; Humans; Influenza, Human; Leukemia; Lymphocytes; Macrophages; Male; Multiple Sclerosis; Myasthenia Gravis; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Sarcoidosis